Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres.

OBJECTIVE: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS: Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

AM-879, a PPARy non-agonist and Ser273 phosphorylation blocker, promotes insulin sensitivity without adverse effects in mice.

Obesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the in vivo effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose. At lower doses, this ligand decreased BAT, increased leptin and Crh expression. However, at a higher dose, it promoted improvement on insulin sensitivity, ameliorates expression of metabolism-related genes, decreased the expression of genes related to liver toxicity, maintaining body weight and adipocyte size. These results present a new lead molecule to ameliorates insulin resistance and confirm AM-879 as a PPARγ non-agonist which blocks Ser273 phosphorylation as a good strategy to modulate insulin sensitivity without developing the adverse effects promoted by PPARγ full agonists.

Wasted leg syndrome: An atypical slowly-progressive form of lower motor neuron disease.

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7-18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patient was later diagnosed with CADASIL. Electromyography (EMG) revealed severe chronic neurogenic changes in proximal leg muscles, and mild changes in distal leg muscles, but EMG of the upper limbs was normal. Upper motor neuron signs were absent clinically and on transcranial magnetic stimulation. This seems to represent a variant of the common wasted-leg syndrome presentation.

Prevalence of Dirofilaria repens in dogs living in deltaic coastal plain of the Volturno River (Italy): a geographical risk model of infection.

The prevalence of vector-associated parasitic infections is high in central-southern Italy. The deltaic coastal plain of the Volturno River has been suspected, by veterinary practitioners, to have a high accidental incidence of Dirofilaria repens. Thus, the goal of this study was to evaluate the prevalence of dirofilariasis and other coinfections frequently described in dogs living in the Volturno area. Blood samples of 100 clinical asymptomatic dogs were examined using a Knott's technique and polymerase chain reaction in order to identify microfilariae. Other vector-borne coinfections were also investigated using ELISA kits. The results were analysed using statistical and Geographic Information System (GIS) software. Microfilariae of D. repens were detected in 10% of the dogs surveyed, with a presence of antibodies against Ehrlichia canis (4/10) and Dirofilaria immitis (1/10). Such high incidence should be considered in light of the zoonotic potential for D. repens and the support for more regular use of repellents to prevent the spread of this disease. The GIS analyses indicated that the study area provides suitable conditions to sustain populations of mosquito vectors and D. repens parasites throughout much of the year.

Validity of computed tomography in diagnosing midfacial fractures.

The aim of this study was to evaluate the sensitivity, accuracy, and reliability of two-dimensional computed tomography (2D-CT) scans (axial, coronal, sagittal planes) and three-dimensional computed tomography (3D-CT) reconstructions in diagnosing midfacial fractures in relation to actual fractures identified clinically and during surgery (gold standard). The imaging diagnosis was performed by a radiologist and an oral and maxillofacial surgeon. Sixty-two patients with a total of 429 midfacial fractures were included. Frontal sinus and nose fractures were easily diagnosed. For the three CT planes, there was a statistically significant difference between the CT examination and the gold standard for five to seven of the nine bones evaluated, while for 3D-CT, a difference was observed only for fractures of the orbital floor. The inter-observer agreement between the oral and maxillofacial surgeon and the radiologist was 75.5%. In conclusion, in this study 3D-CT reconstructions showed significantly the best sensitivity, accuracy, and reliability for the diagnosis of midfacial fractures. The sagittal reconstructions were the least diagnostic of the 2D-CT images. For areas where the parameters studied showed less agreement and hence a more difficult diagnosis, we recommend a combination of 3D and 2D-CT images to improve diagnostic accuracy.

Diagnosis at different stages of paracoccidioidomycosis with oral manifestation: Report of two cases.

Paracocciodiomycosis (PCDM) is a chronic systemic fungal infection, mainly affecting residents and rural workers, being characterized by a long incubation period, which it can take months or years without clinical manifestations, making diagnosis late and difficult. Depending on the stage of the disease, it can cause sequelae and low quality of life, so its correct diagnosis is of great importance for the accurate treatment. Therefore, the aim of this report is to present two cases of diagnosis of patients with PCDM at different stages, who developed chronic manifestations, pain, clinical involvement of the oral cavity and in one case also presented lung injury with fibrosis, as well as to weight loss, dysphagia and cachexia. Both of patients were treated with antifungal therapy and it was observed total remission of the lesions and no recurrences were detected.

Potential Preventive Strategies for Amyotrophic Lateral Sclerosis.

It may seem useless to propose preventive measures for a disease without established pathogenesis and successful therapy, such as amyotrophic lateral sclerosis (ALS). However, we will show that ALS shares essential molecular mechanisms with aging and that established anti-aging strategies, such as healthy diet or individually adjusted exercise, may be successfully applied to ameliorate the condition of ALS patients. These strategies might be applied for prevention if persons at ALS risk could be identified early enough. Recent research advances indicate that this may happen soon.

Cheiloscopy in individuals with Down syndrome and their nonsyndromic biological siblings.

The study aimed to carry out a comparative analysis between the lip print patterns in individuals with Down Syndrome and their nonsyndromic biological siblings. This was a cross-sectional blind study using an inductive approach and extensive direct observation procedures. A total of 68 cheiloscopic charts, named cheilograms, were divided into two groups (n=34), as follows: G1, including Down Syndrome individuals; and G2, including their nonsyndromic siblinggs. The convenience sample was selected in the city of João Pessoa, PB, Brazil. The following features were evaluated in eight labial regions called sub-quadrants: oral commissures (downturned, horizontal and upturned); lip thickness (thin, medium, thick and mixed); and labial grooves (I - complete vertical; I '- incomplete vertical; II - bifurcated; III - criss-cross; IV - reticular; or V - undefined). The data were analyzed by paired Student's t test and McNemar's Chi-square, with a 5% significance level. Most Down Syndrome individuals were found to have downturned oral commissures in 73.5% of cases, while their siblings showed a predominance of horizontal commissures in 73.5% of cases (p=0.009). There was no statistically significant difference for lip thickness between groups. In the analysis of labial groove patterns, Down Syndrome individuals (G1) showed a significant prevalence of the type I pattern (52.2%) as compared to their nonsyndromic siblings (30.1%) (p =< 0.001). Due to the tendency of having vertical labial groove patterns and downturned commissures, Down Syndrome individuals present cheiloscopic differences in relation to their nonsyndromic biological siblings, which suggests that syndromic genetics influences the development of these features. However, this may imply in a reduced potential of cheiloscopic identification due to the low divergence of labial phenotypes among Down Syndrome individuals.

Electric Field Distribution during Non-Invasive Electric and Magnetic Stimulation of the Cervical Spinal Cord.

Experimental studies on transcutaneous spinal cord direct current and magnetic stimulation (tsDCS and tsMS) show promising results in the neuromodulation of spinal sensory and motor pathways, with possible application in spinal functional rehabilitation. Modelling studies on the electric field (EF) distribution during tsDCS and tsMS are powerful tools to understand the underlying biophysics and to select and optimize stimulation protocols for a specific clinical target. The study presented here compares the EF during cervical tsDCS and tsMS. The EF predictions show the same spatial profiles along the cervical spinal cord using both types of stimulation. tsMS presents higher average magnitudes per spinal segment, with a maximum value of 14.61 V/m, whereas tsDCS is approximately 30 times lower, reaching 0.44 V/m. According to previous studies, tsDCS and tsMS induce EF values which are sufficient for spinal neuromodulation.

Muscular cramp: causes and management.

Muscular cramp is a common symptom in healthy people, especially among the elderly and in young people after vigorous or peak exercise. It is prominent in a number of benign neurological syndromes. It is a particular feature of chronic neurogenic disorders, especially amyotrophic lateral sclerosis. A literature review was undertaken to understand the diverse clinical associations of cramp and its neurophysiological basis, taking into account recent developments in membrane physiology and modulation of motor neuronal excitability. Many aspects of cramping remain incompletely understood and require further study. Current treatment options are correspondingly limited.

Epidemiological Data on Anaphylaxis in French Emergency Departments.

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxisrelated codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions.

Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Epidemiological data on anaphylaxis in French emergency departments

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxis-related codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions

ANTECEDENTES: La anafilaxia es un problema prioritario de salud pública en la comunidad mundial alergológica. Sin embargo, los datos epidemiológicos disponibles de morbilidad y mortalidad son mejorables. Presentamos el primer estudio epidemiológico multicéntrico, realizado en siete departamentos de urgencias franceses durante un año, que tuvo como objetivo identificar las cuestiones relevantes para lograr cambios en futuras estrategias, nacionales e internacionales, que deriven en un mejor diagnóstico, tratamiento y prevención de la anafilaxia. MÉTODOS: Se trata de un estudio descriptivo que utilizó la información proveniente de las bases de datos de siete instituciones francesas de salud pública, de la región de Lorena, desde enero hasta diciembre de 2015. Se buscaron nomenclatura y códigos relacionados con la anafilaxia, de la Clasificación Internacional de Enfermedades (CIE-10), y los pacientes fueron validados clínicamente como casos de anafilaxia. RESULTADOS: De los 202.079 ingresos en urgencias, 4.817 tenían códigos relacionados con la anafilaxia CIE-10, 323 de los cuales se validaron clínicamente con el diagnóstico de anafilaxia. Aunque el 45,8% presentó criterios de gravedad, la adrenalina se prescribió solo en el 32,4% de estos casos. En total, 323 casos, el 57,9%, se remitieron posteriormente para un estudio o evaluación alergológica (después o durante la hospitalización) y el 17,3% recibió una receta de adrenalina autoinyectable . CONCLUSIÓN: Según los resultados de este estudio, existe una necesidad urgente e imperiosa de mejorar los planes de salud pública respecto al reconocimiento y tratamiento de la anafilaxia. Los problemas clave detectados en este trabajo, señalan el camino de la toma de decisiones e implementación de acciones de mejora, nacionales e internacionales, para una mejor atención de los pacientes con anafilaxia

Organ and Tissue Donations for Transplants in the Macroregional North of Paraná, Brazil.

BACKGROUND: Few studies have analyzed the results of the organ and tissue donation process for transplants. OBJECTIVES: To analyze donations of organs and tissues for transplants in the Macroregional North of Paraná. MATERIAL AND METHODS: Cross-sectional and retrospective study, using data from 7383 death certificates of eligible donors notified in 2015 by 16 hospitals accredited to the Organ Procurement Organization. The data were analyzed using the prevalence ratio (PR) and the Wald test. RESULTS: Among the 934 eligible donors, the prevalence of effective donations was 23.4% (219) Among the 582 organs and tissues donated, corneas were predominant. Organs became available for donation from younger individuals (PR = 0.992), due to brain death (PR = 2.482), notified by the type III Intra-Hospital Organ and Tissue Donation Commissions for Transplants (PR = 2.016), which took place in intensive care units (PR = 1.471). The relatives interviewed were the partners and/or children (PR = 0.469), and the interviews were held by the nurse (PR = 1.324). CONCLUSION: Effective donations were able to take place through proper organizational structure and trained human resources, highlighting the role of the nurse in the optimization of the organ and tissue donation process for transplants.

Nutraceutical potential of Asparagopsis taxiformis (Delile) Trevisan extracts and assessment of a downstream purification strategy.

The main goal of the present work was to determine the nutraceutical potential of Asparagopsis taxiformis D. extracts from Madeira Archipelago south coast. Extraction methodologies consisted either/or in 72 hours stirring, at room temperature (M1), or 6 cycles of Soxhlet extraction (M2), both with re-extraction. Solvents used were distilled water, ethanol, methanol and ethyl acetate. M1 allowed to obtain the highest values for extraction yield (31.65 g.100g-1 dw) using water, whereas iodine content (3.37 g.100g-1 dw), TPC (1.71 g GAE.100g-1 dw) and chlorophyll a (45.96 mg.100g-1 dw) were obtained using ethanol, and TCC (36.23 mg.100g-1 dw) with methanol. Extracts that showed higher reduction activity in M1 were derived from ethanol extraction (1,908 mg AAE.100g-1 dw). Water and ethanol were the best solvents for higher DPPH scavenging activity in M2, both with same result (IC50 1.37 mg.mL-1). The lowest value of IC50 for chelating activity (1.57 mg.mL-1) was determined in M1, using ethyl acetate. The remaining residue was used to obtain other products, i.e. lipid extraction (M1, 2.05 g.100g-1 dw), carrageenans (M2, 21.18 g.100g-1 dw) and cellulose (M1, 23.81 g.100g-1 dw) with subsequent FTIR ATR analysis. Our results show that A. taxiformis is a valuable source of bioactive compounds. The M1 extraction methodology using ethanol is the most effective solvent to produce an iodine rich bioactive extract with potential of being used as a nutraceutical supplement. Also, we have demonstrated a possible downstream strategy that could be implemented for multiple compound extraction from A. taxiformis residue. This has a vital importance for future feasibility, when using this biomass as an industrial feedstock for multiple products production. Statistical analysis, using SPSS 24.0, was also performed and important correlations were found between assays and methods.

Oral squamous carcinoma cells promote macrophage polarization in an MIF-dependent manner.

BACKGROUND: Tumor-associated macrophages (TAMs) are important determinants of intratumoral immune evasion, neoangiogenesis, extracellular matrix remodeling and dysregulated tumor cell proliferation. Our prior studies revealed that macrophage-derived, but not tumor cell-derived, macrophage migration inhibitory factor (MIF), is an important determinant of TAM alternative activation and M2 polarization. AIM: Because MIF is historically thought to initiate signaling via a receptor-dependent, outside-in mode of action, we wished to investigate the specific contributions of tumor-derived vs. macrophage-derived MIF to M2 marker expression during macrophage polarization. DESIGN: Murine oral squamous cell-carcinoma cells (SCCVII) were co-cultured with either the RAW 264.7 mouse macrophage cell line or mouse primary bone marrow-derived macrophages in the context of MIF genetic loss/inhibition individually or in combination each cell type. METHODS: Twelve well Transwell plates were used to co-culture SCCVII cells and RAW 264.7, MIF+/+ or MIF-/- macrophages treated with/without the small molecule MIF inhibitor, 4-iodo-6-phenylpyrimidine and incubated in the presence or absence of interleukin (IL-4) for 48 h. Macrophages were analyzed by quantitative real-time polymerase chain reaction and/or immunoblotting for relative macrophage polarization marker expression. RESULTS: IL-4 treatment synergizes with SCCVII co-culture in inducing the expression of macrophage M2 markers and loss or inhibition of macrophage-derived MIF significantly reduces both IL-4 alone and IL-4/SCCVII co-culture-induced macrophage M2 marker expression. CONCLUSION: These studies identify an important and dominant requirement for macrophage MIF in maximal Th2-cytokine and oral squamous carcinoma cell-induced macrophage polarization and M2 marker expression.

Hereditary amyloidosis related to transthyretin V30M: disease progression in treated and untreated patients.

BACKGROUND AND PURPOSE: Hereditary amyloidosis related to transthyretin V30M (hATTR V30M) is a progressive length-dependent sensorimotor axonal neuropathy. We aimed to compare the disease progression of treated [liver transplantation (LT) or tafamidis] versus untreated patients with hATTR V30M. METHODS: A total of 81 patients with hATTR V30M were included: 27 untreated, 25 treated with LT and 29 undergoing tafamidis treatment. Neuropathy was assessed at baseline, 12, 24 and 36 months after study entry. We evaluated disease stage, modified polyneuropathy disability (mPND) score and a composite neurophysiological score comprised of sensory and motor conduction parameters. The effect of treatment on disease progression was analysed using linear mixed-effects modelling. RESULTS: At baseline, patients from the untreated group were older (P < 0.01) and those in the LT group had longer disease duration than those in the tafamidis group (P < 0.05). Gender, mPND and motor scores at study entry were equal in the three groups; however, the untreated group had lower sensory scores compared with the tafamidis group (P < 0.01). During the 3-year follow-up period, progression to stage II of the disease was seen only in the untreated group. The progression on mPND, sensory and motor scores was significantly higher in the untreated patients. When treated groups were compared, the LT group had lower rates of composite neurophysiological score progression. However, the sensory score outcome was similar between tafamidis responders and LT patients. CONCLUSION: Both LT and tafamidis therapy modified the natural history of hATTR V30M by reducing neuropathy progression.